Design of an effective vaccine against HIV must take into account the high degree of variability in the sequence of the envelope proteins that have been observed in clinical isolates, and the high mutation rate of the virus. The envelope glycoprotein gpl20 and its precursor gpl60 have been ineffective against clinical isolates of HIV when used as vaccine candidates. HIV-neutralizing antibodies are elicited primarily against the third variable (V3) loop of the sequence. Late in HIV infection, however, neutralizing antibodies with broader strain specificity are produced which appear to be directed at the three-dimensional shape of the CD4 binding site. The investigators hypothesize that this part of gpl20 will make a more effective vaccine antigen than the whole protein. They therefore plan to construct recombinant or synthetic molecules that display this conformation-dependent structure. Their immediate goals are to 1) better define those portions of gpl20 that are involved in binding to CD4; 2) express these gpl20 sequences as part of fusion proteins on the surface of a plant virus and determine which constructs can display the native conformation required for CD4 binding; 3) synthesize the sequences as peptides and model the three-dimensional structure of the CD4 binding epitope using NMR techniques. The structural information obtained from these studies and X-ray crystallography of the recombinant viruses may lead to the design of better recombinant or synthetic antigens that can elicit a more effective immune response to the virus.